Antagonism to sulfathiazole by methylene blue and riboflavin in pneumococcal respiration.

,YIn a previous study (Sevag and Gots, 1948) on the effects of various drugs on the pneumococcal dehydrogenase systems it was found that, whereas acriflavine, atabrine, propamidine, and optochin could inhibit these systems, high concentrations of sulfonamides had no effect. Other investigators (Mellon aind Bambas, 1937; Brazda and Rice, 1942; Fox, 1942; Clifton and Loewinger, 1943) have reported the failure of sulfonamides to inhibit dehydrogenase systems. However, sulfonamides have been shown (Barron and Jacobs, 1937; Chu and Hastings, 1938; Dorfman et al., 1940, 1942; Sevag et al., 1942, 1945) to have a marked effect in inhibiting the aerobic respiration of various organisms. This apparent inconsistency between the effect of sulfonamide on aerobic respiration as measured manometricallyand dehydrogenase activityas measured, usually, by methylene blue reduction required experimental elucidation. Some of these inconsistencies were interpreted (Sevag, 1946) to indicate that methylene blue competed effectively with sulfonamide for flavoprotein and therefore no inhibition of methylene blue reduction could be observed. The data presented here and elsewhere (Sevag and Gots, 1948; Sevag, Gots, and Steers, 1950; Gots and Sevag, 1949) show that methylene blue does antagonize the inhibition of aerobic respiration of pneumococcus, type I, by sulfathiazole, and that, under certain conditions, riboflavin has similar effects. It was also found that inhibition by sulfathiazole of methylene blue reduction can be achieved in systems where the sulfonamide is allowed to react with the cells in the absence of the protecting methylene blue.